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Littauer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014133","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>Prevotella copri<\/jats:italic> (<jats:italic>P copri<\/jats:italic>), a gut commensal, has been reported to be an immune\u2010relevant organism in individuals with rheumatoid arthritis (RA). This study sought to evaluate anti\u2013<jats:italic>P copri<\/jats:italic> (anti\u2013<jats:italic>Pc<\/jats:italic>) antibody responses in our participant cohorts and to determine when in the natural history of RA such responses develop.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed serum levels of immunoglobulin A (IgA) and IgG antibodies from a 27\u2010kd protein of <jats:italic>P copri<\/jats:italic> (anti\u2013<jats:italic>Pc<\/jats:italic><jats:italic>\u2010<\/jats:italic>p27), an immunogenic <jats:italic>P copri<\/jats:italic> protein, in study participants at risk of developing RA, participants who transitioned to RA, participants with early RA (&lt;1 year of disease), and participants with established RA, with comparisons made to their matched controls. We also evaluated anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibody levels in individuals stratified by RA\u2010related autoantibody status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, participants with RA had significantly higher IgA anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibody levels and trended toward higher IgG anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibody levels compared with matched controls. When stratified by early versus established RA, participants with early RA had median IgG anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibody levels that were overall higher, whereas median IgA anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibody levels were statistically significantly higher in participants with established RA compared with their matched controls. In the autoantibody\u2010specific analyses, the at\u2010risk population with anti\u2013cyclic citrullinated peptide (anti\u2010CCP) antibodies, but not rheumatoid factor (RF), trended toward increased levels of IgG anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27. Additionally, RA participants who were seropositive for both CCP and RF had significantly increased levels of IgA anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibodies and trended toward higher levels of IgG anti\u2013<jats:italic>Pc<\/jats:italic>\u2010p27 antibodies compared with matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings support a potential etiologic role for <jats:italic>P copri<\/jats:italic> in both RA preclinical evolution and the subsequent pathogenesis of synovitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42370","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T03:03:15Z","timestamp":1666148595000},"page":"507-516","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Association of Antibodies to <i>Prevotella copri<\/i> in Anti\u2013Cyclic Citrullinated <scp>Peptide\u2010Positive<\/scp> Individuals At Risk of Developing Rheumatoid Arthritis and in Patients With Early or Established Rheumatoid Arthritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5851-7246","authenticated-orcid":false,"given":"Jennifer A.","family":"Seifert","sequence":"first","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Bemis","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Ramsden","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy","family":"Lowell","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Polinski","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Feser","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-7618","authenticated-orcid":false,"given":"Chelsie","family":"Fleischer","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2563-5155","authenticated-orcid":false,"given":"M. Kristen","family":"Demoruelle","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Buckner","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K.","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research and North Shore\u2010Long Island Jewish Health System  Manhasset New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Keating","sequence":"additional","affiliation":[{"name":"University of Chicago  Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-2272","authenticated-orcid":false,"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center and VA Nebraska\u2010Western Iowa Healthcare System  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"O'Dell","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center and VA Nebraska\u2010Western Iowa Healthcare System  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Weisman","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-4861","authenticated-orcid":false,"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Norris","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5268-9853","authenticated-orcid":false,"given":"Allen C.","family":"Steere","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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